EFFECT OF ADJUVANT CHEMOTHERAPY WITH OR WITHOUT ANTHRACYCLINES ON THEACTIVITY AND EFFICACY OF FIRST-LINE CYCLOPHOSPHAMIDE, EPIDOXORUBICIN,AND FLUOROURACIL IN PATIENTS WITH METASTATIC BREAST-CANCER

Purpose: To evaluate the effect of previous adjuvant chemotherapy with or without anthracyclines on overall survival (OS), progression-free survival (PFS), and objective response (OR) rates of metastatic breast cancer patients treated with cyclophosphamide, epidoxorubicin, and fl uorouracil (CEF) as first-line chemotherapy, Patients and Methods: Thr ee-hundred twenty-six assessable metastatic breast cancer patients ent ered onto four consecutive randomized trials performed in our Institut ion and North-West Oncology Group (GONG) cooperative centers from 1983 to 1994. Patients received CEF-based chemotherapy as first-line thera py and were then evaluated, One hundred forty-four patients (44%) did not receive previous adjuvant chemotherapy, and 143 (44%) and 39 (12%) patients received cyclophosphamide, methotrexate, and fluorouracil (C MF)-based and anthracycline-based adjuvant chemotherapy, respectively. Results: ORs to CEF chemotherapy were observed in 161 patients (49.4% ). On univariate analysis, patients who had received prior adjuvant ch emotherapy had a significantly lower probability of response than pati ents who did not: 43% versus 58% (P = .02), No difference between CMF- based (OR rate, 43%) and anthracycline-based (OR rate, 44%) adjuvant c hemotherapy was observed. Stepwise logistic regression analysis indica ted that adjuvant chemotherapy (P = .005), bone as dominant metastatic site (P = .02), and previous hormonotherapy for metastatic disease (P = .005) were the most important factors in predicting a poor OR rate, The median PFS and OS times of the whole group were 9.8 and 17.9 mont hs, respectively. Patients who did not receive adjuvant chemotherapy h ad ct longer survival time (21.1 months) compared with patients previo usly treated with CMF-based (15.3 months) or anthracycline-based (15.8 months) adjuvant chemotherapy, Multivariate analysis confirmed adjuva nt chemotherapy to be among the strongest prognostic factors associate d with both a poor PFS and OS. Conclusion: Previous adjuvant chemother apy adversely affects OR, PFS, and OS in metastatic breast cancer pati ents treated with the CEF regimen as first-line chemotherapy. No diffe rence was observed between patients previously treated with CMF-based or anthracycline-based adjuvant chemotherapy.